Research Papers:

Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21WAF1/CIP1 and p27KIP1 pathway

Santosh Kumar Singh, Saswati Banerjee, Edward P. Acosta, James W. Lillard and Rajesh Singh _

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Oncotarget. 2017; 8:17216-17228. https://doi.org/10.18632/oncotarget.15303

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Santosh Kumar Singh1, Saswati Banerjee1, Edward P. Acosta2, James W. Lillard1, Rajesh Singh1

1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA

2Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence to:

Rajesh Singh, email: [email protected]

Keywords: cell cycle, resveratrol, docetaxel, p21, p53

Received: December 10, 2016     Accepted: January 24, 2017     Published: February 13, 2017


Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis. In C4-2B cells the combination up regulated the expression of p53, and cell cycle inhibitors (p21WAF1/CIP1, p27KIP), which, in turn, inhibited the expression of CDK4, cyclin D1, cyclin E1 and induced hypo-phosphorylation of Rb thus blocking the transition of cells in the G0/G1 to S phase. In contrast, the synergistic effect was not profound in DU145 due to its lesser sensitivity to DTX. The suppression of cyclin B1 and CDK1 expression in both cell lines inhibits the further progression of cells in G2/M phase. The current study demonstrates that combination treatment blocks the cell cycle arrest by modulation of key regulators and promotes apoptosis via p53 dependent and independent mechanism in PCa.

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